The field of quantum computing has grown from concept to demonstration devices over the past 20 years. Universal quantum computing offers efficiency in approaching problems of scientific and ...commercial interest, such as factoring large numbers, searching databases, simulating intractable models from quantum physics, and optimizing complex cost functions. Here, we present an 11-qubit fully-connected, programmable quantum computer in a trapped ion system composed of 13
Yb
ions. We demonstrate average single-qubit gate fidelities of 99.5Formula: see text, average two-qubit-gate fidelities of 97.5Formula: see text, and SPAM errors of 0.7Formula: see text. To illustrate the capabilities of this universal platform and provide a basis for comparison with similarly-sized devices, we compile the Bernstein-Vazirani and Hidden Shift algorithms into our native gates and execute them on the hardware with average success rates of 78Formula: see text and 35Formula: see text, respectively. These algorithms serve as excellent benchmarks for any type of quantum hardware, and show that our system outperforms all other currently available hardware.
Quantum fluctuations of the electromagnetic vacuum are responsible for physical effects such as the Casimir force and the radiative decay of atoms, and set fundamental limits on the sensitivity of ...measurements. Entanglement between photons can produce correlations that result in a reduction of these fluctuations below the ordinary vacuum level, allowing measurements that surpass the standard quantum limit in sensitivity. The effects of such 'squeezed states' of light on matter were first considered in a prediction of the radiative decay rates of atoms in squeezed vacuum. Despite efforts to demonstrate such effects in experiments with natural atoms, a direct quantitative observation of this prediction has remained elusive. Here we report a twofold reduction of the transverse radiative decay rate of a superconducting artificial atom coupled to continuum squeezed vacuum. The artificial atom is effectively a two-level system formed by the strong interaction between a superconducting circuit and a microwave-frequency cavity. A Josephson parametric amplifier is used to generate quadrature-squeezed electromagnetic vacuum. The observed twofold reduction in the decay rate of the atom allows the transverse coherence time, T2, to exceed the ordinary vacuum decay limit, 2T1. We demonstrate that the measured radiative decay dynamics can be used to reconstruct the Wigner distribution of the itinerant squeezed state. Our results confirm a canonical prediction of quantum optics and should enable new studies of the quantum light-matter interaction.
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IJS, KISLJ, NUK, UL, UM, UPUK
Abdominal aortic aneurysm (AAA) is a complex disease which is incompletely accounted for. Basement membrane (BM) Collagen IV (COL4A1/A2) is abundant in the artery wall, and several lines of evidence ...indicate a protective role of baseline COL4A1/A2 in AAA development. Using Col4a1/a2 hemizygous knockout mice (Col4a1/a2
, 129Svj background) we show that partial Col4a1/a2 deficiency augmented AAA formation. Although unchallenged aortas were morphometrically and biomechanically unaffected by genotype, explorative proteomic analyses of aortas revealed a clear reduction in BM components and contractile vascular smooth muscle cell (VSMC) proteins, suggesting a central effect of the BM in maintaining VSMCs in the contractile phenotype. These findings were translated to human arteries by showing that COL4A1/A2 correlated to BM proteins and VSMC markers in non-lesioned internal mammary arteries obtained from coronary artery bypass procedures. Moreover, in human AAA tissue, MYH11 (VSMC marker) was depleted in areas of reduced COL4 as assessed by immunohistochemistry. Finally, circulating COL4A1 degradation fragments correlated with AAA progression in the largest Danish AAA cohort, suggesting COL4A1/A2 proteolysis to be an important feature of AAA formation. In sum, we identify COL4A1/A2 as a critical regulator of VSMC phenotype and a protective factor in AAA formation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Pancreatic cancer, a highly aggressive tumour type with uniformly poor prognosis, exemplifies the classically held view of stepwise cancer development. The current model of tumorigenesis, based on ...analyses of precursor lesions, termed pancreatic intraepithelial neoplasm (PanINs) lesions, makes two predictions: first, that pancreatic cancer develops through a particular sequence of genetic alterations (KRAS, followed by CDKN2A, then TP53 and SMAD4); and second, that the evolutionary trajectory of pancreatic cancer progression is gradual because each alteration is acquired independently. A shortcoming of this model is that clonally expanded precursor lesions do not always belong to the tumour lineage, indicating that the evolutionary trajectory of the tumour lineage and precursor lesions can be divergent. This prevailing model of tumorigenesis has contributed to the clinical notion that pancreatic cancer evolves slowly and presents at a late stage. However, the propensity for this disease to rapidly metastasize and the inability to improve patient outcomes, despite efforts aimed at early detection, suggest that pancreatic cancer progression is not gradual. Here, using newly developed informatics tools, we tracked changes in DNA copy number and their associated rearrangements in tumour-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumours harbour complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors is the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set-off invasive cancer growth. These findings challenge the current progression model of pancreatic cancer and provide insights into the mutational processes that give rise to these aggressive tumours.
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IJS, KISLJ, NUK, SBMB, UL, UM, UPUK
Mining causes extensive damage to aquatic ecosystems via acidification, heavy metal pollution, sediment loading, and Ca decline. Yet little is known about the effects of mining on freshwater systems ...in the Southern Hemisphere. A case in point is the region of western Tasmania, Australia, an area extensively mined in the 19th century, resulting in severe environmental contamination. In order to assess the impacts of mining on aquatic ecosystems in this region, we present a multiproxy investigation of the lacustrine sediments from Owen Tarn, Tasmania. This study includes a combination of radiometric dating (14C and 210Pb), sediment geochemistry (XRF and ICP-MS), pollen, charcoal and diatoms. Generalised additive mixed models were used to test if changes in the aquatic ecosystem can be explained by other covariates. Results from this record found four key impact phases: (1) Pre-mining, (2) Early mining, (3) Intense mining, and (4) Post-mining. Before mining, low heavy metal concentrations, slow sedimentation, low fire activity, and high biomass indicate pre-impact conditions. The aquatic environment at this time was oligotrophic and dystrophic with sufficient light availability, typical of western Tasmanian lakes during the Holocene. Prosperous mining resulted in increased burning, a decrease in landscape biomass and an increase in sedimentation resulting in decreased light availability of the aquatic environment. Extensive mining at Mount Lyell in the 1930s resulted in peak heavy metal pollutants (Pb, Cu and Co) and a further increase in inorganic inputs resulted in a disturbed low light lake environment (dominated by Hantzschia amphioxys and Pinnularia divergentissima). Following the closure of the Mount Lyell Co. in 1994 CE, Ca declined to below pre-mining levels resulting in a new diatom assemblage and deformed diatom valves. Therefore, the Owen Tarn record demonstrates severe sediment pollution and continued impacts of mining long after mining has stopped at Mt. Lyell Mining Co.
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•Mining has caused extensive environmental degradation in Tasmania.•A palaeoenvironmental study investigated the impacts of mining on an aquatic ecosystem.•The Owen Tarn record revealed four key impact phases.•Pre-mining, Early mining, Intense mining, and Post mining impacts.•Owen Tarn is impacted by severe sediment pollution and Ca decline from mining.
The Owen Tarn record revealed four impact phases: Pre-mining, Early mining, Intense mining, and Post mining. Mining caused severe sediment pollution and Ca decline in the aquatic environment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Ices are the main carriers of volatiles in protoplanetary disks and are crucial to our understanding of the protoplanetary disk chemistry that ultimately sets the organic composition of planets. The ...Director’s Discretionary-Early Release Science (DD-ERS) program Ice Age on the
James Webb
Space Telescope (JWST) follows the ice evolution through all stages of star and planet formation. JWST’s exquisite sensitivity and angular resolution uniquely enable detailed and spatially resolved inventories of ices in protoplanetary disks. JWST/NIRSpec observations of the edge-on Class II protoplanetary disk HH 48 NE reveal spatially resolved absorption features of the major ice components H
2
O, CO
2
, and CO, and multiple weaker signatures from less abundant ices NH
3
, OCN
−
, and OCS. Isotopologue
13
CO
2
ice has been detected for the first time in a protoplanetary disk. Since multiple complex light paths contribute to the observed flux, the ice absorption features are filled in by ice-free scattered light. This implies that observed optical depths should be interpreted as lower limits to the total ice column in the disk and that abundance ratios cannot be determined directly from the spectrum. The
12
CO
2
/
13
CO
2
integrated absorption ratio of 14 implies that the
12
CO
2
feature is saturated, without the flux approaching zero, indicative of a very high CO
2
column density on the line of sight, and a corresponding abundance with respect to hydrogen that is higher than interstellar medium values by a factor of at least a few. Observations of rare isotopologues are crucial, as we show that the
13
CO
2
observation allowed us to determine the column density of CO
2
to be at least 1.6 × 10
18
cm
−2
, which is more than an order of magnitude higher than the lower limit directly inferred from the observed optical depth. Spatial variations in the depth of the strong ice features are smaller than a factor of two. Radial variations in ice abundance, for example snowlines, are significantly modified since all observed photons have passed through the full radial extent of the disk. CO ice is observed at perplexing heights in the disk, extending to the top of the CO-emitting gas layer. Although poorly understood radiative transfer effects could contribute to this, we argue that the most likely interpretation is that we observed some CO ice at high temperatures, trapped in less volatile ices such as H
2
O and CO
2
. Future radiative transfer models will be required to constrain the physical origin of the ice absorption and the implications of these observations for our current understanding of disk physics and chemistry.
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FMFMET, NUK, UL, UM, UPUK
Summary
B‐1 and B‐2 B cell subsets carry out a diverse array of functions that range broadly from responding to innate stimuli, antigen presentation, cytokine secretion and antibody production. In ...this review, we first cover the functional roles of the major murine B cell subsets. We then highlight emerging evidence, primarily in preclinical rodent studies, to show that select B cell subsets are a therapeutic target in obesity and its associated co‐morbidities. High fat diets promote accumulation of select murine B cell phenotypes in visceral adipose tissue. As a consequence, B cells exacerbate inflammation and thereby insulin sensitivity through the production of autoantibodies and via cross‐talk with select adipose resident macrophages, CD4+ and CD8+ T cells. In contrast, interleukin (IL)‐10‐secreting regulatory B cells counteract the proinflammatory profile and improve glucose sensitivity. We subsequently review data from rodent studies that show pharmacological supplementation of obesogenic diets with long chain n‐3 polyunsaturated fatty acids or specialized pro‐resolving lipid mediators synthesized from endogenous n‐3 polyunsaturated fatty acids boost B cell activation and antibody production. This may have potential benefits for improving inflammation in addition to combating the increased risk of viral infection that is an associated complication of obesity and type II diabetes. Finally, we propose potential underlying mechanisms throughout the review by which B cell activity could be differentially regulated in response to high fat diets.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Context. Phosphorus-bearing compounds have only been studied in the circumstellar environments of the asymptotic giant branch star IRC +10 216 and the protoplanetary nebula CRL 2688, both carbon-rich ...objects, and the oxygen-rich red supergiant VY CMa. The current chemical models cannot reproduce the high abundances of PO and PN derived from observations of VY CMa. No observations have been reported of phosphorus in the circumstellar envelopes of oxygen-rich asymptotic giant branch stars. Aims. We aim to set observational constraints on the phosphorous chemistry in the circumstellar envelopes of oxygen-rich asymptotic giant branch stars, by focussing on the Mira-type variable star IK Tau. Methods. Using the IRAM 30 m telescope and the Submillimeter Array, we observed four rotational transitions of PN (J = 2−1,3−2,6−5,7−6) and four of PO (J = 5/2−3/2,7/2−5/2,13/2−11/2,15/2−13/2). The IRAM 30 m observations were dedicated line observations, while the Submillimeter Array data come from an unbiased spectral survey in the frequency range 279−355 GHz. Results. We present the first detections of PN and PO in an oxygen-rich asymptotic giant branch star and estimate abundances X(PN/H2) ≈ 3 × 10-7 and X(PO/H2) in the range 0.5−6.0 × 10-7. This is several orders of magnitude higher than what is found for the carbon-rich asymptotic giant branch star IRC +10 216. The diameter (≲0.′′7) of the PN and PO emission distributions measured in the interferometric data corresponds to a maximum radial extent of about 40 stellar radii. The abundances and the spatial occurrence of the molecules are in very good agreement with the results reported for VY CMa. We did not detect PS or PH3 in the survey. Conclusions. We suggest that PN and PO are the main carriers of phosphorus in the gas phase, with abundances possibly up to several 10-7. The current chemical models cannot account for this, underlining the strong need for updated chemical models that include phosphorous compounds.
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FMFMET, NUK, UL, UM, UPUK
Oncogenic KRAS is the key driver oncogene for several of the most aggressive human cancers. One key feature of oncogenic KRAS expression is an early increase in cellular reactive oxygen species (ROS) ...which promotes cellular transformation if cells manage to escape cell death, mechanisms of which remain incompletely understood. Here, we identify that expression of oncogenic as compared to WT KRAS in isogenic cellular systems renders cells more resistant to ferroptosis, a recently described type of regulated necrosis. Mechanistically, we find that cells with mutant KRAS show a specific lack of ferroptosis-induced lipid peroxidation. Interestingly, KRAS-mutant cells upregulate expression of ferroptosis suppressor protein 1 (FSP1). Indeed, elevated levels of FSP1 in KRAS-mutant cells are responsible for mediating ferroptosis resistance and FSP1 is upregulated as a consequence of MAPK and NRF2 pathway activation downstream of KRAS. Strikingly, FSP1 activity promotes cellular transformation in soft agar and its overexpression is sufficient to promote spheroid growth in 3D in KRAS WT cells. Moreover, FSP1 expression and its activity in ferroptosis inhibition accelerates tumor onset of KRAS WT cells in the absence of oncogenic KRAS in vivo. Consequently, we find that pharmacological induction of ferroptosis in pancreatic organoids derived from the LsL-KRAS
expressing mouse model is only effective in combination with FSP1 inhibition. Lastly, FSP1 is upregulated in non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC) as compared to the respective normal tissue of origin and correlates with NRF2 expression in PDAC patient datasets. Based on these data, we propose that KRAS-mutant cells must navigate a ferroptosis checkpoint by upregulating FSP1 during tumor establishment. Consequently, ferroptosis-inducing therapy should be combined with FSP1 inhibitors for efficient therapy of KRAS-mutant cancers.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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